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Safety, penetration and efficacy of topically applied bevacizumab: evaluation of eyedrops in corneal neovascularization after chemical burn
Author(s) -
Yoeruek Efdal,
Ziemssen Focke,
HenkeFahle Sigrid,
Tatar Olcay,
Tura Aysegül,
Grisanti Salvatore,
BartzSchmidt Karl U.,
Szurman Peter
Publication year - 2008
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1600-0420.2007.01049.x
Subject(s) - bevacizumab , corneal neovascularization , medicine , cornea , neovascularization , corneal epithelium , ophthalmology , vascular endothelial growth factor , angiogenesis , surgery , chemotherapy , vegf receptors
. Purpose: That vascular endothelial growth factor (VEGF) plays a major role in inflammatory angiogenesis has been well established. This pilot study was designed to evaluate experimental treatment with bevacizumab eyedrops in corneal neovascularization induced by alkali burn. The feasibility of topical administration, corneal cell viability and corneal penetration were investigated in an animal model. Methods: Eighteen chinchilla bastard rabbit corneas injured with 1 m NaOH were divided into three groups: untreated, early and late treatment groups. Eyedrops of bevacizumab solution (25 mg/ml) were administered five times daily. Clinical examination under stereoscopic microscope was performed to evaluate corneal opacity, neovascularization, vessel size and oedema. Histopathology was analysed for vessel density and apoptotic reaction. Additionally, intracameral bevacizumab concentration was measured with enzyme‐linked immunosorbent assay (ELISA) after repeated topical applications. Results: A fast increase in aqueous bevacizumab concentration was achieved when the solution was instilled every minute onto a healthy eye surface. As well as clear anti‐angiogenic effects, anti‐fibrotic effects were also seen after corneal burn, maintaining corneal transparency. Early treatment of actively growing vessels showed a significantly better outcome, although apoptosis of pre‐existing vessels could also be induced by the late treatment. No specific toxicity was seen regarding epithelium, keratocytes or endothelium. Conclusions: The data from this pilot study suggest that bevacizumab eyedrops can sufficiently penetrate the corneal stroma and anterior chamber. When administered soon after alkali burn, bevacizumab seems to significantly reduce corneal damage. Combinations of established treatment regimens with topical bevacizumab might be considered in severe injuries with otherwise devastating prognoses.